Endocrine Crises. Fred Pieracci, MD, MPH TACS Fellow

Transcription

1 Endocrine Crises Fred Pieracci, MD, MPH TACS Fellow

2 Endocrine Crises Rare Highly lethal Elusive Easily treatable

3 1. Thyroid 1. Thyroid storm 2. Myxedema coma Outline 2. Parathyroid: 1. Severe hypercalcemia secondary to 3 hyperparathyroidism 3. Adrenal 1. Addisonian crisis 2. Steroids in septic shock 3. Pheochromocytoma crisis

4 Thyroid Hormone Physiology Tyrosine Dietary Idodide Thyroid peroxidase PTU Monoiodotyrosine (MIT) Diiodotyrosine (DIT) Thyroid Peripheral tissues T 4 NaI Steroids T 3

5 Thyroid Storm Exacerbation of hyperthyroidism in response to metabolic stress (e.g., trauma, surgery, critical illness) First recognized during thyroidectomy in unprepped Grave s patients Uncommon Life-threatening (mortality 20%)

6 Thyroid Storm Classic Presentation Fever (106 F) Abnormal mental state (anxiety coma) Diagnosis unlikely if normal mentation High-output cardiac failure: Tachyarrthymias, CHF GI distress TSH undetectable; T3 > T4 WBC, LFTs, calcium, glucose

7 Thyroid Storm Atypical Presentations Normothermia, normoglycemia, lactic acidosis, MODS Elderly: Apathetic storm; weakness and emotional apathy

8 Thyroid Storm Treatment Prevention Adequate preparation of patient undergoing surgery for hyperthyroidism Best indicator of appropriate preparation for surgery: TSH T3 is the most important number to assess in patients who require surgery relatively quickly

9 Thyroid Storm Treatment Inhibit hormone synthesis: PTU 1000 mg load then 300 mg PO q6h Blunt end-organ effects: Beta blocker: Propranolol vs. esmolol 250 mcg/kg load then 50 mcg/kg/min Inhibit hormone release: NaI 500 mg IV q8h Inhibit peripheral conversion: Dexamethasone 2 mg q6 Treat precipitating problem

10 Myxedema Coma Exacerbation of hypothyroidism in response to metabolic stress (e.g., trauma, surgery, critical illness) Long-standing, neglected, untreated hypothyroidism Uncommon (1:1,000,000); Predominantly elderly women presenting in the winter Life-threatening (mortality 50%) Sunitinib (Sutent)

11 Hypothermia T<35ºC Myxedema Coma Symptoms/Diagnosis Disorientation coma Non-pitting total body edema Macroglossia Ileus Bradycardia heart block Free T 4 < 10 mcg/dl TSH usually increased but unreliable (1º vs. 2º hypothyroidism) Anemia, hyponatremia, hypoglycemia

12 Myxedema Coma Treatment Levothyroxine (T 4 ) Bolus mcg IV Maintainence mcg until symptoms resolve Support organ failure Coexisting glococorticoid deficiency common (~33%); give steroids

13 Sick Euthyroid Syndrome? Pathologic vs. adaptation to critical illness Progressive, sub-acute deterioration of thyroid function Early: decreased peripheral conversion of T4 T3, usually iatrogenic (medication induced) Late: Reduced concentrations of TSH, T4, & T3 Treatment unclear

14 Myedema Coma Thyroid Storm Sick Euthyroid Mild Mod Severe TSH - T4 - T3

15 PTH Ca +2 PO 4-2 BONE Stimulate osteoclasts GUT VitD-mediated Ca +2 absorption Vit D KIDNEY Activation of VitD Ca +2 PO 4-2 Ca +2 Ca +2 PO -2 4 Ca +2 resorption PO 4-2 resorption PO 4-2

16 Hyperparathyroidism Primary: Pathology originates within the parathyroid gland(s); Adenoma (85%), hyperplasia (15%), carcinoma (1%). Secondary: Overzealous response to hypocalcemia of non-parathyroid etiology, most commonly renal failure. Resolves with resolution of non-parathyroid pathology. Tertiary: Chronically stimulated gland(s) develop autonomous function despite resolution of nonparathyroid pathology. *Severe hypercalcemia*

17 Shock fluid sequestration hypoprotienemia, hypocalcemia Acute renal failure Vit D hydoxylation, Ca reabsorption Secondary tertiary hypoparathyroidism with severe hypercalcemia Presents as refractory hypercalcemia, bradycardia, asystole

18 Severe Hypercalcemia Treatment Volume Expansion Diuresis urine output 250ml/hr Begin only after adequate hydration has been achieved Definitive therapy = bisphosphonates Pamidronate 90 mg IV (maximal effect takes 72 hours).

19 Adrenal Insufficiency Common in critical illness (as high as 77% in septic shock) Etiology Iatrogenic Persists for over a year Infection (Sepsis) Suppression Destruction via massive adrenal hemorrhage (Waterhouse-Friderichsen Syndrome) Trauma

20 Adrenal Insufficiency Diagnosis Hypotension despite adequate fluid resuscitation and vasopressor therapy Hypoglycemia, hyponatremia, hyperkalemia Biochemical Assays: Random cortisol < 20 mcg/dl Cortisol stimulation test: increase < 9 mcg/dl Free vs. total Etomidate suppresses HPA axis

21 Adrenal Insufficiency Treatment Hydrocortisone mg /day Do not wait for the labs to come back Probably don t need to taper if < 7 days? retest after steroids discontinued

22 Steroids in Septic Shock Where do we stand? Annane et al. JAMA 2002 Hypotension for 1 hour despite adequate fluid resuscitation and vasopressor therapy Randomization within 3 hours of shock onset Hydrocortisone 50 mg IV q6, fludrocortisone 50 mcg IV qd x 7 days 300 patients, 77% non-acth responders Significant mortality reduction overall (61% vs. 55%), driven by non-responders (63% vs. 53%).

23 Steroids in Septic Shock Where do we stand? Sprung et al. NEJM 2008 Need for vasopressor for at least 1 hour Randomization within 72 hours of shock onset Hydrocortisone 50 mg IV q6 x 5 days, then tapered 500 patients, 47% non-acth responders No mortality reduction (~35%/group) regardless of response to ACTH-stimulation. More superinfection in the steroid group

24 Steroids in Septic Shock Where do we stand? Surviving Sepsis Guidelines 2008

25 Catecholamine Synthesis Any Chromaffin Tissue Tyrosine Thyroid hydroxylase STEROIDS Dopamine Urine Norepinephrine Normetanephrine Adrenal Medulla PNMT VMA Epinephrine Metanephrine

26 Pheochromocytoma Crisis Rapid, massive release of catecholamines resulting in cardiovascular collapse More often triggered vs. spontaneous Stressor (e.g., trauma, surgery, anesthesia, critical illness) Medications Glucocorticoids Beta blockers

27 Pheochromocytoma Crisis Diagnosis Classically, HTN with triad of headache, palpitations, diaphroresos Cardiogenic shock/myocardial ischemia Pulmonary edema, respiratory failure Rhabdomyolysis/renal failure Tachyarrythmias Elevated 24-hour urine metanephrines/vma Plasma metanephrine/normetanephrine

28 Pheochromocytoma Crisis Treatment Volume expansion Alpha blockade Beta blockade Surgical extirpation

29 2001

30 Increased circulating cortisol helps maintain hemodynamic stability in the face of surgical stress Patients treated with long term exogenous steroids have a blunted HPA response to surgical stress Case reports have led to the longstanding (>50 years) surgical tenant of stress dose steroids.

31 Risks of Corticosteroids Infection Hypergylcemia Impaired wound healing Psychosis Pancreatitis Neuromuscular atrophy

32 Systematic review of Medline, Cochrane Library, Best Evidence, and Cancerlit databases from Jan 1966 September Original research focusing on human patients treated with steroids who were undergoing an operative procedure. One outcome measure had to be blood pressure. Methodological quality assessed using the Heyland Criteria.

33 4, articles Variable patient populations, extent of surgery, definitions of outcomes 2/11 randomized

34 2/11 (n=89 & 104): Steroids withheld in the perioperative period 2% required rescue steroids for refractory hypotension 2/11 (n=18 & 20): Randomized to stress dose vs. preoperative dose Cardiac and renal transplantation All patients had adrenal suppression (ACTH stim test) No difference in outcomes (BP, HR, hypotensive crisis)

35 3/11 (n=21, 28, & 84): Followed patients maintained on preoperative doses No adverse consequences 1/11 (n=61): Non-randomized single stress dose vs. preoperative dose No difference in need for a rescue dose to treat unexplained hypotension

36 GRADE C: All patients treated with corticosteroids should be treated with perioperative glucocorticoids at the time of operation GRADE B: Patients should be maintained on their preoperative daily dose of steroids throughout the perioperative period Authors are currently conducting an adequately-powered RCT involving IBD patients